Adenovirus vectors have shown promise for vaccines, but one key hurdle is preexisting immunity to these viruses in humans. The VRC has been investigating the use of prime/boost strategies using DNA, nanoparticles, proteins and adenovirus vaccines and the use of alternate adenoviral serotypes or modified adenoviral vectors to overcome prior immunity. During the past year, the VRC has tested rAd expressing HIV outer domain (OD) proteins as the prime and boost for generating VRC01 like neutralizing antibodies in humanized mice and were able to demonstrate that a heterologous prime and boost regimen using recombinant chimp adenovirus vectors (rChAd3 OD) is superior than a DNA/rAd5 regimen in generation of neutralizing antibodies in mice. In addition, evaluation of chimpanzee adenovirus vectors (ChAd3 and ChAd63) to analyze their ability to induce an immune response as compared to Ad5 and in the presence of Ad5 seropostivity for Ebola, influenza and RSV is ongoing. Several of these vectors are being further tested to evaluate their potential use in clinical trials. Plans are in progress to produce cGMP lots of a ChAd Ebola vaccine.